Rapid adipose tissue expansion induces proliferation of memory adipose tissue T cells

Abstract Obesity is recognized as a pro-inflammatory state featuring immune dysregulation and metabolic disease. Obesity-induced inflammation is observed in the adipose tissue of humans and mice. Adipose tissue T cells (ATTs) are dynamically shifted from Th2 cells in the lean state to an influx of CD8+ and Th1 T cells that promote adipose tissue inflammation in the obese state. Knowing this, many gaps remain in our understanding of ATT generation, maintenance, expansion, and regulation in adipose tissue. Specifically, it is unknown if naïve T cells are recruited to and stimulated within adipose tissue or if resident memory ATTs, which are abundant in the lean state, are stimulated during the initiation of the obese state. We hypothesized that memory ATTs respond to the early fat expansion elicited upon obesity induction. To test this, we used a short-term DIO male mouse model and assessed ATT proliferation during high-fat diet (HFD) feeding. Mice on HFD gained significantly more total body, epidydimal white adipose tissue (eWAT), and inguinal WAT (iWAT) weight compared to normal diet mice. We observed no increase in frequency or proliferation of naïve ATTs with HFD. Conversely, we observed significant proliferation of memory ATTs with 1 week of HFD in the eWAT, iWAT and omental WAT. This proliferation was restored to normal diet levels by 2 weeks of HFD. These data suggest that memory ATTs uniquely and intensely respond to signals present during HFD-induced rapid adipose tissue expansion. Ongoing studies seek to determine if there are sex differences by examining ATT dynamics in female mice. Further, we seek to determine which signal(s) drive memory ATT proliferation to identify targets to suppress ATT initiation of obesity-associated inflammation. Supported by grants from NIH (K12 GM111725, R01 DK090262).